Study On Quality Assessment And Analytical Method In Vivo Of Shen Mai Injection

Objective...For the problems in development, production and clinical use of traditional Chinese medicine injection(TCMI), the topics regard Shen Mai injection as the research object to carry out quality assessment study by comparing the content of ginsenoside Rg1, Re and the difference of HPLC fingerprint Chromatographic peak area in different manufacturers and batches of Shen Mai injection, so as to standardize the quality standards and provide some basis for the quality control of Shen Mai injection; At the same time, carry out pharmacokinetics and serum chemistry studies on Shen Mai injection of oral and intravenous administration two different administration routes to establish bio-analysis methods of Shen Mai injection, investigate the efficacy and safety, guide rational clinical drug use, and create new research and development ideas of TCMI, in additional, provide scientific theoretical guidance for research and development, production and application.Methods...①High performance liquid chromatography (HPLC) method was used to determine and compare the content of ginsenoside Rg1and Re in Shenmai injection from ten batches of the same manufacturer and five different manufacturers;②Compare the variation of HPLC profiles characteristics from different manufacturers and the same manufacturers of different batches of Shen Mai injection, and analyz the similarity by similarity analyzing software;③Determine the plasma concentration that given Shen Mai injection in two different ways at different time points by HPLC method, then calculate pharmacokinetic parameters with pharmacological software DAS3.0, and calculate oral bioavailability;④Establish HPLC maps of Shen Mai injection, blank serum, oral administration serurn and intravenous administration serum to compare and analyze differences in peak or chemical composition.Results...①The content of ginsenoside Rg1and Re in Shenmai injection are uneven. just as there are certain differences between different batches of the same manufacturer Shen mai injection, but diversity of ginsenoside Rg1and Re content in Shenmai injection is great;②There is a big difference in the number of peaks and peak area of Shen Mai injection from different manufacturers. The peak numbers in ten batchs of the same Shen Mai injection manufacturer are almost same, however, the peak areas are certain different but relatively small compared to the former;③Ginsenoside Rg1, Re in Shen Mai injection metabolic faster by intravenous administrating, and it is difficult to measure in plasma after6h; But it is slow by oral administration, and reach peak concentration at8h, the oral bioavailabilitis were7.22%,7.16%respectively;④We found6value target components in rat serum, in which Ginsenoside Rg1(peak3), ginsenoside Re (peak4) come into the blood as prototype, peak15is the natural substances of blood; and found5kinds of common components between intravenous and oral administrating serum, namely, peak3, peak4, peak5, peak8and peak11;9kinds of components were found in administrating serum.Conclusion...The subject established a comprehensive study method on Shen Mai injection and provide a certain foundation for post-marketing re-evaluation.①There are obvious differences in the content of index composition and fingerprint characteristic of Shen Mai injection from different manufacturers, so we should reduce the quality control range of index components specified in the quality standards of Shen Mai injection, and strictly control the consistency of raw materials and production processes.②Shen Mai injection was absorbed slowly by oral administrating with low bioavailability, but intravenous administration manifests its superiority of fast onset by directly injected into blood vessels.③Through reaserching on serum chemistry, ingredients in intravenous serum were more than oral serum, and the extra ingredients were suspected to be ingredients which cause adverse reactions. A new idea of the development of TCMI was found by designing TCM injections refining process in accordance with the ingredients of oral administration.④We suggest carrying out pharmacokinetics and serum chemistry research on all traditional Chinese medicine injection.